Duke named to national network that will research hard-to-diagnose medical cases– The News & Observer

DURHAM — The National Institutes of Health has picked Duke University and five other medical and research institutions to create a new, federally-sponsored network to fight diseases that have proven unusually difficult to identify.

Duke won a $7.2 million grant from the National Institutes of Health spread over four years for its role in the new Undiagnosed Diseases Network. The network will help individual patients whose cases have become medical mysteries and also help discover new diseases and gain a better understanding of the clues to both rare and common disorders.

Duke’s role in the network will build on its early expertise in what is a fast-emerging type of medicine. A team of clinicians and genetics researchers there have worked together solving the mysteries of such cases for more than four years.

“Duke has quite a long history of integrating really contemporary genomics with clinical care,” said David Goldstein, director of Duke’s Center for Human Genome Variation and a principal investigator in Duke’s grant to join the network. “We’ve been at it quite awhile, and because we got started early we’ve learned some things during these years – things to be careful of and how to do it well.”

The NIH already had a program that worked on such cases, but decided to expand that into a national network.

The approach works. The NIH’s program, which began in 2008, has enrolled about 600 patients with unidentified illnesses and has been able to diagnose about 100 of them and has discovered two previously unknown diseases. And Duke’s program has been able to diagnose about 37 percent of the more than 100 patients it has seen so far, said Dr. Vandana Shashi, a medical geneticist and the other principal investigator for Duke’s grant proposal.

Among Duke’s success stories is 22-month-old Cara Greene, whose family moved from Raleigh to Wilmington last month.

This winter, her parents noticed Cara’s eyes were moving in an odd, jittery way. Then she developed worse symptoms, losing the strength in her legs and arms and repeatedly falling flat on her face.

At Duke, one alarming potential cause, a brain tumor, was quickly ruled out. But eventually all that was left as the likely cause was an immune disorder, treatable with a form of chemotherapy with major potential side effects.

Her medical team, though, called Shashi, who recommended genetic sequencing. Duke expedited that testing because of the possibility of chemotherapy, said Cara’s mother, Kristen.

On the April day Cara’s parents were to meet with a medical team to discuss plans for the chemotherapy, the genetics team called. It had found the mutation responsible for her symptoms. Cara had a rare condition, Brown-Vialetto-Van-Laere syndrome, that in many cases can be treated with vitamin B2.

Cara started getting the vitamin treatment the next day. Within a week, she began improving and is now walking better and has gained strength in her arms.

It’s hard to overestimate the relief parents feel when they finally get a diagnosis for something that baffles doctors, even if the prognosis is grim, said Kristen Greene. And in Cara’s case, it saved her life, as she likely would have died without proper treatment.

“We were so terrified about finding a genetic cause because we thought that would mean her disease would be untreatable,” Greene said. “But the fact that she has something that’s not only treatable, but treatable with just a vitamin, is like a miracle to us.”

Benefits of working together

Each of the institutions chosen for the new consortium had to have clinical and genetic research capabilities, Shashi said. But they also have some different strengths, she said. For example, Duke has more expertise in pediatrics than some, while others may have an expertise in a niche such as diseases caused by environmental exposure.

“So, it’s complimentary, but at the same time, everybody can do what is needed,” Shashi said.

A central committee will decide where it makes the best sense, based on both geography and the strengths of the different sites, to send a specific patient.

Doctors in the new network will collect and share clinical and laboratory data, including genomic information, clinical observations and documentation of environmental exposures. The network also will develop common protocols aimed at improving the level of diagnosis and care for patients with undiagnosed diseases.

Goldstein said it will be terrific not only to have more funding for the work, but also to have the other resources that the network will bring.

Scale in such work is particularly important, he said, because one of the ways researchers know they have found the likely cause of a patient’s disease is by seeing the same thing in more than one case. A large network will obviously increase the likelihood of that.

“Also, we’ll have the benefit of a lot of bright people working together and as a group trying to refine the basic rules for how we do this kind of work, because this is new territory,” Goldstein said. “When you sequence a new patient’s genome, sometimes you get a relatively clear answer, but sometimes you just get a hint, and it’s reassuring to have a team of people involved that you can bounce ideas off of and try to come up with some collective rules that make sense.

“It’s really about learning to do this work well,” he said. “This is a new way of working, and right now, the community is in the process of really erasing the distinction between genomics research and clinical care.”

Besides Duke, the other members of the network are Baylor College of Medicine; Harvard Teaching Hospitals through the Boston Children’s Hospital, Brigham and Women’s Hospital, and Massachusetts General Hospital; Stanford University; the University of California, Los Angeles; and Vanderbilt University Medical Center.